TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13953	42082;42083;42084	chr2:178635467;178635466;178635465	chr2:179500194;179500193;179500192
N2AB	12312	37159;37160;37161	chr2:178635467;178635466;178635465	chr2:179500194;179500193;179500192
N2A	11385	34378;34379;34380	chr2:178635467;178635466;178635465	chr2:179500194;179500193;179500192
N2B	4888	14887;14888;14889	chr2:178635467;178635466;178635465	chr2:179500194;179500193;179500192
Novex-1	5013	15262;15263;15264	chr2:178635467;178635466;178635465	chr2:179500194;179500193;179500192
Novex-2	5080	15463;15464;15465	chr2:178635467;178635466;178635465	chr2:179500194;179500193;179500192
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-89
• Domain position: 78
• Structural Position: 163
• Q(SASA): 0.5783
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
R/I	rs1268324463	0.573	0.126	N	0.412	0.22	0.353336612579	gnomAD-2.1.1	4.21E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.39E-05	None	0	0	0
R/I	rs1268324463	0.573	0.126	N	0.412	0.22	0.353336612579	gnomAD-4.0.0	3.21587E-06	None	None	None	None	N	None	0	0	None	0	2.80081E-05	None	0	0	0	1.45075E-05	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
R/A	0.9507	likely_pathogenic	0.9065	pathogenic	-0.759	Destabilizing	0.855	D	0.444	neutral	None	None	None	None	N
R/C	0.7591	likely_pathogenic	0.633	pathogenic	-0.852	Destabilizing	0.999	D	0.387	neutral	None	None	None	None	N
R/D	0.9844	likely_pathogenic	0.9682	pathogenic	-0.1	Destabilizing	0.99	D	0.504	neutral	None	None	None	None	N
R/E	0.9067	likely_pathogenic	0.8351	pathogenic	0.069	Stabilizing	0.935	D	0.448	neutral	None	None	None	None	N
R/F	0.9638	likely_pathogenic	0.92	pathogenic	-0.357	Destabilizing	0.99	D	0.455	neutral	None	None	None	None	N
R/G	0.9445	likely_pathogenic	0.8915	pathogenic	-1.095	Destabilizing	0.956	D	0.5	neutral	D	0.560760352	None	None	N
R/H	0.5469	ambiguous	0.3732	ambiguous	-1.307	Destabilizing	0.997	D	0.419	neutral	None	None	None	None	N
R/I	0.7671	likely_pathogenic	0.6061	pathogenic	0.158	Stabilizing	0.126	N	0.412	neutral	N	0.507691084	None	None	N
R/K	0.494	ambiguous	0.3589	ambiguous	-0.672	Destabilizing	0.126	N	0.232	neutral	N	0.500786852	None	None	N
R/L	0.7907	likely_pathogenic	0.6649	pathogenic	0.158	Stabilizing	0.747	D	0.409	neutral	None	None	None	None	N
R/M	0.8794	likely_pathogenic	0.7604	pathogenic	-0.435	Destabilizing	0.99	D	0.471	neutral	None	None	None	None	N
R/N	0.9595	likely_pathogenic	0.9205	pathogenic	-0.48	Destabilizing	0.967	D	0.458	neutral	None	None	None	None	N
R/P	0.9713	likely_pathogenic	0.9499	pathogenic	-0.127	Destabilizing	0.997	D	0.469	neutral	None	None	None	None	N
R/Q	0.5122	ambiguous	0.3547	ambiguous	-0.471	Destabilizing	0.98	D	0.433	neutral	None	None	None	None	N
R/S	0.9685	likely_pathogenic	0.9288	pathogenic	-1.169	Destabilizing	0.844	D	0.511	neutral	D	0.558348619	None	None	N
R/T	0.8818	likely_pathogenic	0.7404	pathogenic	-0.801	Destabilizing	0.126	N	0.343	neutral	N	0.491927477	None	None	N
R/V	0.8433	likely_pathogenic	0.7221	pathogenic	-0.127	Destabilizing	0.161	N	0.401	neutral	None	None	None	None	N
R/W	0.7351	likely_pathogenic	0.6151	pathogenic	-0.042	Destabilizing	0.999	D	0.405	neutral	None	None	None	None	N
R/Y	0.8761	likely_pathogenic	0.779	pathogenic	0.211	Stabilizing	0.997	D	0.477	neutral	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.